Insulin-like growth factor binding protein-2 (IGFBP-2) is a 36,000 dalton protein that is a member of the IGFBP family. There are six forms of high affinity IGF binding proteins. In addition to binding the insulin-like growth factors I and II and acting as transport proteins, these proteins have been shown to have some actions that are independent of their ability to bind to IGFs.
IGFBP-2 is the second most abundant binding protein in serum. It circulates in concentrations in humans that vary between 100-600 ng/ml. Protein concentrations are high during fetal life and at birth and fall progressively during childhood and adolescence. There is a slight rise, an approximately 25% increase that occurs between 60-80 years. Serum concentrations of IGFBP-2 are regulated by hormones and nutrients. Fasting causes a significant increase in IGFBP-2 and feeding (particularly feeding protein) restores concentrations to normal. Concentrations are also suppressed by administration of insulin or growth hormone, and are increased by insulin-like growth factor-I. This is probably due in part to suppression of growth hormone and insulin, both of which are suppressed by administering IGF-I.
Proteolytic cleavage of IGFBP-2 results in small fragments that include the heparin binding domain (HBD). A small molecule containing the HBD present in the linker region of IGFBP-2 has been synthesized. Of the two HBDs in this molecule, the one synthesized is unique to IGFBP-2 and is not represented in other IGFBPs.
The present invention overcomes previous shortcomings in the art by providing peptides of IFGBP-2 and methods of their use in treating bone disorders, controlling weight and improving bone marrow reconstitution.